|FABURAY, BONTO - Kansas State University|
|LEBEDEV, MAXIM - South Dakota State University|
|MOROZOV, IGOR - Kansas State University|
|YOUNG, ALLAN - South Dakota State University|
|RICHT, JUERGEN - Kansas State University|
Submitted to: Vector-Borne and Zoonotic Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/24/2014
Publication Date: 10/17/2014
Citation: Faburay, B., Lebedev, M., Mcvey, D.S., Wilson, W.C., Morozov, I., Young, A., Richt, J.A. 2014. A Glycoprotein Subunit Vaccine Elicits a Strong Rift Valley Fever Virus Neutralizing Antibody Response in Sheep. Vector-Borne and Zoonotic Diseases. 14(10):746-756. DOI: 10.1089/vbz.2014.1650
Interpretive Summary: Vaccination approaches to control mosquito-borne virus Rift Valley fever have limitations due to safety concerns. The virus causes severe to lethal disease in domestic ruminants and man and is endemic in Sub-Saharan Africa. There also are concerns that the virus could be accidentally introduced into non-endemic countries. This paper describes the evaluation of a new, safe subunit vaccine candidate using recombinantly produce viral proteins.
Technical Abstract: Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the presence of susceptible vectors in non-endemic countries has created increased interest in RVF vaccines. A milestone in vaccine development is the use of specific virus proteins expressed in eukaryotic or prokaryotic expression systems to elicit neutralizing antibodies in susceptible hosts. Herein, we expressed RVFV structural proteins, N-terminus glycoprotein (Gn) and C-terminus glycoprotein (Gc), using a recombinant baculovirus expression system, and reconstituted them as Gn and Gc in a subunit vaccine formulation for evaluation of immunogenicity in a natural host species, sheep. Six sheep were each immunized with a primary dose of 50 ug of the vaccine adjuvanted with montanide ISA2S, and at day 21 post-vaccination, each animal received a second dose of the same vaccine. The vaccine induced strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA). Plaque reduction neutralization test (PRNT80) showed the primary dose of the subunit vaccine was sufficient to elicit protective virus neutralizing antibody liters ranging from 1:40 to 1:160, and the second vaccine dose boosted the titer to more than 1:1,280. ELISA and immunblot analyses using the RVFV recombinant nucleocapsid protein as a negative diagnostic marker antigen indicated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible and represents a promising vaccine platform for RVFV infection in susceptible host species.